Long-Term Effects of Antidepressants: What Research Shows

Anyone who’s ever taken antidepressants for an extended period of time has probably wondered whether they’ll experience long-term effects:

• After years of antidepressant use, will I be worse off?
• What effects on my mind and body will I experience?
• Can I ever stop taking antidepressants?

These are just a few of the many questions patients face when their doctor tells them to keep taking a medication such as an antidepressant or when they’ve had difficulty stopping an antidepressant.

With an estimated 13.2% of American adults having taken an antidepressant in the last 30 days, according to 2015-2018 data from the U.S. Centers for Disease Control and Prevention, questions about the long-term effects of antidepressants are relevant to a growing number of people. Young people are among those taking antidepressants as well. From 2016 through 2022, antidepressant prescriptions for young adults and teens rose more than 66%, a study published in the American Academy of Pediatrics’ Journal, Pediatrics, found.

What the research shows

Concerns about long-term antidepressant use have been raised in recent years. In 2022, for example, researchers from the University of Bristol found that long-term use (defined as 5 or 10 years) might double the risk of heart disease.

At the same time, stopping antidepressant use after years can carry a greater risk of depression returning or worsening, according to another study published in The New England Journal of Medicine.

This study looked at 478 patients who had been taking antidepressants for at least two years or had a history of at least two prior episodes of depression. All patients indicated feeling well enough to consider stopping taking their antidepressant. The results of this study showed that when patients stopped their antidepressant, they were more likely to experience a relapse of depression and more symptoms of depression and/or anxiety.

“Quality-of-life measures and symptoms of depression, anxiety and medication withdrawal were generally worse in patients who discontinued their antidepressant therapy,” the study concluded.

Patients taking antidepressants for years are often left wondering what to make of findings such as these. Many have seen the benefits of taking medication for depression, while still experiencing effects.

Among a group of 180 patients in New Zealand who had taken antidepressants for three to 15 years, nearly nine in 10 said antidepressants had improved their symptoms, according to findings published in the Patient Preference and Adherence journal. These patients also reported side effects such as withdrawal symptoms (74%), sexual problems (72%), weight gain (65%), feeling emotionally numb (65%), and feeling addicted (43%). Additionally, some participants noted having problems trying to discontinue their antidepressants.

The importance of discussing with your doctor

Until more is known, mental health professionals say it’s best for patients and their doctors to weigh the potential impact of long-term antidepressant use against the risk of relapse of depression.

In addition, clinicians should review medication use with their patients more frequently. Antidepressant use too often goes on autopilot, especially if it’s working, according to a 2019 article in The Wall Street Journal.

“Sometimes a person gets put on a medicine and it simply gets continued because nobody thinks very hard about it,” Dr. James Potash, psychiatrist-in-chief at Johns Hopkins Medicine, said in the story. The article described a 2014 study in the medical journal Family Practice that showed reviews of medications and doses were less likely to occur the longer a patient is on an antidepressant.

The science behind antidepressant use

Antidepressants work by impacting brain chemistry. The most commonly prescribed antidepressants work to increase the level of chemical messengers known as neurotransmitters, for example serotonin and norepinephrine.

According to an article on the WebMD website, the following types of antidepressants are often used:

• SSRIs, or selective serotonin reuptake inhibitors. They block serotonin from being reabsorbed by nerve terminals in the brain. SSRIs typically have fewer side effects than certain other types of antidepressants and are commonly the first type prescribed to new patients. They tend to start working within one to four weeks and may require taking up to 12 weeks for the full benefit.
• SNRIs, or serotonin and norepinephrine reuptake inhibitors. These help boost two neurotransmitters (serotonin and norepinephrine), though not always equally. Full effects typically are felt within six to eight weeks.
• NDRIs, or norepinephrine and dopamine reuptake inhibitors. They help keep higher levels of both norepinephrine and dopamine in the brain. 
• Cyclic antidepressants. First used in the 1950s, they impact a broader range of brain chemicals than newer medications and typically have more serious side effects. Doctors tend not to use cyclic antidepressants unless other drugs haven’t worked.
• SARIs, or serotonin antagonist and reuptake inhibitors. In addition to preventing the reuptake of serotonin, these medications can redirect serotonin to other locations in the brain, helping regulate mood.
• MAOIs, or monoamine oxidase inhibitors. MAOIs block a protein in the brain called monoamine oxidase. This action prevents the brain from breaking down serotonin and other neurotransmitters, but these medications can have serious side effects and have a higher potential for overdose.

Each class of antidepressant has a list of side effects that patients might experience. Side effects may occur over a short time frame or be associated with long-term use. Some patients experience significant side effects, while others don’t have any.

Antidepressant withdrawal

For some patients, discontinuing an antidepressant brings on withdrawal symptoms. A 2017 survey of 250 U.S. patients “with a diagnosis of serious mental illness and a recent goal to stop up to two prescribed psychiatric medications, which they had taken for at least nine months,” for example, found that 54% rated their withdrawal effects as severe. The survey results, reported in Psychiatric Services journal, also found that nearly three-quarters of respondents wanted to discontinue their medication at least in part because of the perceived long-term effects of using antidepressants.

The Mayo Clinic website advises patients who are interested in stopping their antidepressant to discuss it with their doctor. While antidepressants aren’t addictive, they can create a physical dependence in some patients.

“Stopping treatment abruptly or missing several doses can cause withdrawal-like symptoms, and quitting suddenly may cause a sudden worsening of depression,” the Mayo Clinic website says. “Work with your doctor to gradually and safely decrease your dose.”

What you can do if you’re taking antidepressants long-term

In the 2019 story in The Wall Street Journal, Beth Salcedo, a psychiatrist serving as president of the Anxiety and Depression Association of America, provided the following suggestions to patients on long-term antidepressant use:

• “Check in with your doctor regularly – at least twice a year – to assess whether the drug is still needed or working, or if the does needs adjusting.”
• “If you decide to stop the medication, do it under a doctor’s guidance and taper it very slowly – over a few months or longer – to minimize withdrawal symptoms and make it easier to reverse course if anxiety or depression surges.”
• “Do a course of cognitive behavioral therapy before or while going off medication. This can give you skills to manage anxiety and depression and can help prevent a relapse.”
• “Identify early warning signs that a relapse may be on the horizon, like difficulty sleeping or avoiding social engagements, so you can quickly adjust or restart treatment.”

For more information about this topic and other topics, please visit: 

https://genesight.com/blog/patient/depression-diagnosis-treatment-and-beyond/

https://genesight.com/blog/patient/antidepressant-withdrawal-what-to-know/

https://genesight.com/blog/patient/what-does-clinical-depression-feel-like/